Washington, DC USA (UroToday.com) Dr. Donna Hansel presented variant morphology in bladder cancer during today’s general session of the 2015 Society of Urologic Oncology Meeting. Emerging molecular data is based on existing classification schemes, and this could potentially trump the current morphological data we have.

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Immunophenotype may also provide information in the future. The list of variants in bladder cancer is long, and as of now, we don’t have molecular data on most of these variants. An important question in pathology is, at what point do molecular changes become an emerging variant? To answer this, it’s important to first have a grasp on common variants and emerging phenotypes seen in practice.

Urothelial cancer accounts for more than 90% of bladder cancer pathology in the US, followed by squamous (5%), adenocarcinoma (2%), and small cell (<1%). Variants may morphologically resemble any tumor in the body and can develop immunomarkers consistent with the morphology. The most common variant is urothelial carcinoma w divergent differentiation. Of this variant, squamous differentiation is most common (20-40%) followed by glandular (6-20%) and trophoblastic differentiation (rare). The challenge in identifying variants lies in the subjectivity of the diagnosis along with the relative paucity of specific markers.

Dr.. Hansel covered the extensive list of urothelial carcinoma variants beyond those with divergent differentiation. Nested Urothelial carcinoma is being increasingly recognized and is often misdiagnosed on biopsy due to shallow resection and bland morphology. It features small and large nests with small tubules and minimal atypia, and is often diagnosed on slices involving invasive disease. Micropapillary disease is increasingly being recognized as an aggressive variant, and institutions are more frequently offering early cystectomy for these patients. It features small nests with clusters of tumor cells, and has a 5-year survival of 24% (vs 51% in classic urothelial). One major issue in the diagnosis of micropapillary disease is the low degree of interobserver agreement (kappa = 0.54), likely due to the variability in morphology. Of note, HER2 gene amplification occurs frequently in micropapillary bladder cancer. Lymphoepithelial-like cancer looks like a head and neck tumor, and under the microscope it appears to be an inflammatory nodule. It is pleomorphic and has vesicular nuclei with prominent nucleoli. In its pure form, patients may have better outcomes than those with pure urothelial disease. Plasmacytoid urothelial cancer mimics the appearance of plasma cells with an eccentrically placed nucleolus; signet ring morphology is also included in this category. Peritoneal carcinomatosis has been described, and accordingly, this variant is associated with poor outcomes. Carcinosarcoma is an epithelial derived tumor with regions that mimic sarcoma. Patients with this variant frequently have less than 1 year survival.

Most variants discussed do not occur in pure form, and can be admixed, which begs the question, does the proportion of variant matter? Also, how different does a variant need to be in order to warrant its own classification? Our challenge going forward, given the relative rarity of each variant, is to identify objective data (including genomic profiling) that can answer these questions.